Pressure induced structural changes and dimer destabilization of HIV-1 protease studied by molecular dynamics simulations

Abstract

High-pressure methods became an attractive tool of investigation of structural stability of proteins.Besides protein unfolding, dimerization can be studied this way, too. HIV-1 protease is a convenient target of experimental and theoretical high-pressure studies. In this study molecular-dynamics simulations are used to predict the response of HIV-1 protease to the pressure of 0.1 to 600 MPa.The protease conformation of both monomer and dimer is highly rigid changing insignificantly with growing pressure. Hydrophobicity of the protease decreases with increasing pressure. Water density inside the active-site cavity grows from 87% to 100% of the bulk water density within the pressure range. Dimer-dissociation volume change is negative values for most of the pressure range with the minimum of -105 ml/mol, except a short interval of positive values at low pressures. The dimer is thus slightly stabilized up to 160 MPa, but strongly destabilized by higher pressures.

Equilibria of oligomeric proteins under high pressure – A theoretical description

“…equilibria between the highest oligomer and the monomer without any intermediate states) of homooligomers of any degree, heterodimer and heterotrimers, and consecutive equilibria (containing intermediate oligomers of lower degree than the highest one) of homo-and heterotrimer. In all the cases only pressureindependent negative volume changes of oligomer dissociations will be considered as it seems to be a good approximation supported by the overall experimental evidence as well as our recent theoretical simulation (Kutalkova et al, 2014).…”